A major mission of this group involves the basic research and service functions of NMR instrumentation provided to NIDDK scientists of the Laboratory of Bioorganic Chemistry, Laboratory of Medicinal Chemistry, other NIH laboratories and, to a limited extent, to scientists of other institutes. Four instruments (a 500 MHz, a 600 MHz and two 300 MHz) are now in full operation and have been widely used by investigators from different laboratories. These spectrometers are now connected to the NIDDK network. Investigators can access the NMR data from their PCs via a secure file transfer protocol and process NMR data using independent NMR software. Collaborative research projects that use two higher field instruments include 1) structural determination of two major alkaloids in Melanophryniscus toads (Anura, Bufonidae) as indolizidine 239Q and quinolizidine 275I (in collaboration with Dr. John Daly's work group), 2) conformational studies of structurally alatered DNA-resulting from chemcial modification by diolepoxides formed from know chemical corcinogens, such as benzoapyrene (BaP) (in collaboration with Dr. Donald Jerina's group) and 3) conformational studies of agonist and antagonist of nucleotide P2Y receptors. A number of methanocarba analogues, which have a fused cyclopropane ring at the C4 and C5 of a 5 member-ring moiety of the carbocyclic neucleoside, are known to enhance potency toward many P2Y receptors. Our NMR results show that these methanocarba analogues adopt predominantly (>93%) an N-state (C2-exo) conformation, thus, supporting the notion that a (N)-conformation over a (S)-conformation at the 5 member-ring moiety is the major cause for the potency enhancement.